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DEMS > Unit 4 week 2 > Flashcards

Unit 4 week 2 Flashcards

1
Q

Presentation of adrenal insufficiency (BOTH primary and secondary adrenal insufficiency)

A

1) Hyponatremia
2) Hypotension
3) Hypovolemia
4) Tachycardia
5) Hypoglycemia
6) Eosinophilia

+ fatigue, weakness, postural dizziness, anorexia, nausea, vomiting, diarrhea, abdominal pain, weight loss, myalgias, arthralgias, headache

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2
Q

Presentation of adrenal insufficiency ONLY present with primary AI

A

1) Hyperkalemia
2) Hyperpigmentation
3) Salt craving

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3
Q

Adrenal Crisis

symptoms (6) and treatment

A

EMERGENCY

-nausea, vomiting, fever, syncope, hypotension, tachycardia

GIVE STRESS DOSE STEROIDS (Hydrocortisone 100 mg IV every 8 hrs)

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4
Q

Tests for diagnosis of adrenal insufficiency (4)

A

1) Cortisol level (7-8am cortisol not > 16-18 → check ACTH with cortrosyn)

2) Cortrosyn (synthetic ACTH): stimulation test of adrenal reserve
- Baseline serum cortisol + IV injection of ACTH → serum cortisol at 30 and 60 minutes

3) Adrenal CT scan
4) Serum ACTH level

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5
Q

Primary vs. Secondary Adrenal Insufficiency

A

Primary = adrenal gland is not producing cortisol

Secondary = any cause upstream of adrenals

  • ACTH NOT being produced
  • adrenals are normal and respond normally to AGII –> normal aldo levels
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6
Q

Causes of Primary adrenal insufficiency

A

1) Addison’s Disease (autoimmune destruction)
2) Infectious - TB (most common cause in developing countries), Fungi, HIV
3) Amyloid infiltration of adrenals
4) Hemorrhagic, Metastatic, Surgical destruction of adrenals

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7
Q

Presentation of Primary adrenal insufficiency (4)

A

1) Hyponatremia
2) Hyperkalemia
3) Hypotension
4) Hyperpigmentation

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8
Q

Why do patients with primary AI have hyperkalemia? Why do they have hyperpigmentation?

A

Hyperkalemia due to lack cortisol AND ALDOSTERONE → hyponatremia, hyperkalemia

Hyperpigmentation due to Increased POMC (large ACTH precursor molecule)
–> increased ACTH and MSH (melanocyte stimulating hormone)

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9
Q

Diagnosis of Primary AI

4 tests and their findings

A

1) *Serum cortisol < 5ug/dL at baseline
2) *Plasma ACTH > 100 pg/ml
3) *Serum cortisol < 20ug/dl after Cosyntropin (ACTH stim test)

4) Adrenal CT Scan:
Small glands → autoimmune, metabolic
Large glands → all other causes

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10
Q

Treatment of primary adrenal insufficiency

A

glucocorticoids and mineralocorticoid replacement

  • Hydrocortisone or prednisone (GC)
  • Fludrocortisone (MC)
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11
Q

Causes of secondary adrenal insufficiency (3)

A

1) Supraphysiological exogenous glucocorticoids for > 3 weeks
2) Opioids
3) Hypothalamic/pituitary lesions (tumor, surgery, radiation, infection, hemorrhage, infiltrative, metastatic)

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12
Q

Presentation of secondary adrenal insufficiency

A

1) Hyponatremia
2) Hypotension, hypovolemia
3) NORMOkalemic (preserved aldo synthesis)
4) Low ACTH
5) No hyperpigmentation

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13
Q

Diagnosis of secondary adrenal insufficiency (4)

tests + results

A

1) Serum cortisol < 5ug/dl baseline
2) Serum cortisol < 20ug/dl after Cosyntropin (chronic secondary AI - may have normal ACTH response if this is new onset of AI and adrenals haven’t atrophied)
3) Plasma ACTH low or normal
4) MRI pituitary may show pathology

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14
Q

Treatment of secondary adrenal insufficiency

A

replace GCs only

No MC replacement required

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15
Q

Adrenal medullary catecholamines synthesis

what is rate limiting step?
what step does cortisol effect?

A

Tyrosine → DOPA (via tyrosine hydroxylase = RATE LIMITING STEP)

DOPA → DA → NE

NE → epinephrine (via PNMT = UPREGULATED BY CORTISOL)

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16
Q

Pheochromocytoma

A

Tumor of dark chromaffin cells → excess NE and epinephrine

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17
Q

Paraganglioma

A

pheochromocytoma outside the adrenal medulla

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18
Q

Genetics of pheochromocytoma

A

commonly associated with genetic abnormalities and familial syndromes

MEN (2A, 2B) - Ret gene mutation
VHL
NF-1

SDHB
SDHD

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19
Q

SDHB vs. SDHD genes in pheochromocytoma

A

SDHB = gene that significantly increases risk for malignant pheochromocytoma

  • Dopamine secreting tumor associated with malignancy
  • B FOR BAD

SDHD = AD, paternal inheritance
D FOR DAD

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20
Q

RET gene and pheochromocytoma

A

mutated in MEN2A, 2B

RET cell surface receptor somatic mutation → constitutive activation

Glial-derived neurotrophic growth factor (GDNF) binds RET → intracellular signaling stimulating cell synthesis of NE and EPI

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21
Q

Constellation of findings in: MEN2A (3)

A

Pheochromocytoma
Medullary thyroid carcinoma (Calcitonin-secreting C cells)
Hyperparathyroidism

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22
Q

Constellation of findings in: MEN2B (3)

A

Pheochromocycoma
Medullary thyroid carcinoma
Mucosal neuromas

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23
Q

Constellation of findings in: VHL (6)

A 
pheochromocytoma
RCC
renal/pancreatic cysts
CNS hemangioblastomas
islet cell tumors
retinal angiomas
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24
Q

Constellation of findings in: NF-1 (5)

A 
pheochromocytoma
hyperparathyroidism
duodenal carcinoids
medullary thyroid carcinoma
optic nerve tumors
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25
Q

Clinical manifestations of pheochromocytoma

triad of symptoms + 3 other findings

A

TRIAD = headache, palpitations, diaphoresis

Hypertension (a1 vasoconstriction)
-Severely resistant to treatment

Increased HR, sweating and tremulousness (B1 receptors increase inotropic and chronotropic heart effects)

Vasodilation in muscle beds (B2 receptors)

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26
Q

Diagnosis of pheochromocytoma (3 tests)

A

1) 24 hour urinary collection
2) CT/MRI to localize tumor
3) I-123 MIBG scan: localization for extra-adrenal, recurrent, and metastatic tumors

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27
Q

24 hour urine collection in pheochromocytoma

A
  • Catecholamines (Epi, NE) –> Not as reliable, needle stick can cause a rush of catecholamines
  • Metabolites (metanephrines, normetanephrines, VMA) (can do serum also)
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28
Q

Medications that can interfere with 24 hr urine levels of catecholamines and metabolites (4)

A

Interfering medications: can falsely elevate catecholamines / metabolites

Acetaminophen
SSRIs, SNRIs
Marijuana and other illicit drugs

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29
Q

Treatment of pheochromocytoma

A

1) Surgical removal
2) Alpha-adrenergic blocker (phenoxybenzamine)

3) B-blocker (labetalol)
DO NOT start B-blocker before a-blocker

4) Ca2+ channel blocker

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30
Q

Licorice ingestion and hyperaldosteronism?

A

(pseudohypoaldosteronism): licorice prevents inactivation of cortisol in kidney
→ HTN and hypokalemia

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31
Q

Causes of secondary aldosteronism (2)

A

Cirrhosis

Heart failure

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32
Q

Primary aldosteronism (Conn’s Syndrome)

A

Adrenal cortex (glomerulosa) primarily secretes too much aldosterone

  • Low renin and angiotensin II (under normal feedback mechanisms)
  • RAAS feedback loop is perturbed

Most common cause of secondary hypertension

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33
Q

Primary aldosteronism (Conn’s Syndrome)

Presentation (6)

A

1) Resistant hypertension
- HTN at a young age, HTN resistant to multiple anti HTN meds, stage 2 HTN (>160/100)

2) Hypokalemia - may be very severe or normal
3) Metabolic alkalosis
4) Muscle weakness
5) Mild hypernatremia
6) Presence of adrenal adenoma possible

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34
Q

Primary aldosteronism (Conn’s Syndrome)

Diagnosis (4)

A

1) Aldosterone:Renin Ratio: ratio > 20
- High plasma aldosterone, low plasma renin

2) IV saline suppression test
-IV saline should suppress aldosterone, but if they have primary aldosteronism → no aldo suppression
Aldo > 10 ng/dL confirms dx

3) CT or MRI to look for adenoma or hyperplasia
4) Adrenal Vein Sampling (AVS) for lateralization (look for difference in aldosterone levels between R and L adrenal vein)

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35
Q

Which medications should be stopped before getting plasma renin and aldosterone levels?

A

Must STOP interfering medications before testing (spironolactone, eplerenone)

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36
Q

Treatment of primary aldosteronism

A

Surgical cure

Bilateral adrenal hyperplasia or non-surgical candidate → treat with mineralocorticoid antagonist (spironolactone or eplerenone)

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37
Q

4 types of primary aldosteronism

A

1) Aldosterone producing adenoma (34%)
2) Idiopathic hyperaldosteronism (bilateral adrenal hyperplasia) (66%)
3) Glucocorticoid remediable hyperaldosteronism
4) Aldosterone-producing carcinoma

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38
Q

Glucocorticoid remediable hyperaldosteronism

mechanism?

A

genetic rearrangement fusing regulatory promoter of 11-B hydroxylase with structural component of aldosterone synthase → aldosterone synthase under positive control of ACTH

–> increased aldosterone synthesis in response to ACTH

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39
Q

3 main categories of Cushing’s Syndrome

A

1) Iatrogenic (chronic administration of GCs - most common)
2) ACTH dependent
3) ACTH independent: high cortisol production, low ACTH, feedback mechanism still works

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40
Q

Causes of ACTH dependent Cushing’s Syndrome

A

1) Pituitary adenoma (Cushing’s Disease)

2) Ectopic ACTH Syndrome (small cell lung cancer)

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41
Q

Pituitary adenoma (Cushing’s Disease)

ACTH and cortisol levels

A

High ACTH, high cortisol

Feedback mechanism does not turn off ACTH

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42
Q

Ectopic ACTH Syndrome

ACTH and cortisol levels

A

VERY high ACTH, VERY high cortisol

Feedback mechanism does not turn off ACTH

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43
Q

Causes of ACTH independent Cushing’s Syndrome

A

Adrenal Adenoma
Adrenal Carcinoma
Nodular Adrenal Hyperplasia

high cortisol production, low ACTH, feedback mechanism still works

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44
Q

3 steps for working up Cushing’s syndrome

A

1) Establish patient has Cushing’s syndrome

2) Determine etiology of hypercortisolism
ACTH level (ACTH dependent vs. independent)

3) 3) Determine if ACTH is ectopic or from pituitary

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45
Q

Tests that can establish if a patient has Cushing’s syndrome (3)

A

1) 24 hr urinary free cortisol
2) 1 mg dexamethasone suppression test (cortisol should be low after dexamethasone)
3) Midnight salivary cortisol elevated (cortisol should be LOWEST at midnight)

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46
Q

What test can distinguish between ACTH dependent vs. independent Cushing’s Sydrome

A

ACTH level

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47
Q

How can you determine if ACTH production is ectopic or from pituitary? (3 tests)

A

1) CT, MRI, ultrasonography, isotope scanning
2) 8 mg dex suppression test
3) Inferior petrosal sinus sampling

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48
Q

8 mg dex suppression test - for what? tells you what?

A

determine if ACTH production is ectopic or from pituitary

Pituitary source: cortisol suppresses to < 5 ng/dL because still some sensitivity of pituitary corticotroph cells

Not very reliable

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49
Q

Inferior petrosal sinus sampling

A

measure baseline ACTH at intervals after stimulation with CRH

Pit source → ACTH should be higher in petrosal sinus than central IVC

Ectopic source → ACTH similar in sinus and central IVC

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50
Q

Adrenal incidentalomas

A

adrenal gland tumors are common, most clinically insignificant, majority are non-functioning

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51
Q

Initial evaluation of Adrenal incidentalomas must exclude:

A

1) Benign or Malignant? Radiographic appearance

2) Functional or nonfunctional?

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52
Q

Determining benign or malignant nature of adrenal incidentaloma

Malignant: size? shape? lipid density? signal intensity?

Benign:
< \_\_\_\_\_\_\_ size
\_\_\_\_\_\_\_ with \_\_\_\_\_\_\_\_ borders
HU is \_\_\_\_\_\_ on noncontrast CT
\_\_\_\_\_\_\_ lipid content
\_\_\_\_\_\_\_\_\_\_ occurs on out of phase imaging
A

Malignant: Large, irregular, lipid-poor lesion with higher signal intensity (high HU, > 10)

Benign:
-< 4 cm in size
-Homogenous with smooth/regular borders
-HU < 10 on non-contrast CT
-High intracellular lipid content, density closer to water and fat
-Signal dropout on out of phase imaging
Rapid enhancement of contrast, rapid loss of contrast (>50% washout)

MRI is as effective as CT scanning for distinguishing benign from malignant lesions

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53
Q

Adrenal incidentalomas

Functional or nonfunctional?

what tests should you order to determine this? (3)

A

1) Plasma metanephrines or 24 hr urine mets/cats
SCREEN FOR PHEOCHROMOCYTOMA

2) 1 mg overnight dex suppression test
SCREEN FOR HYPERCORTISOLISM

3) If patient is hypertensive, screen for primary aldosteronism with aldosterone/plasma renin level

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54
Q

Adrenocorticosteroids:

____________ effects can NOT be separated from anti-inflammatory effects and ___________ effects cannot be separated from immunosuppressive effects

A

Metabolic effects can NOT be separated from anti-inflammatory effects and anti-inflammatory effects can NOT be separated from immunosuppressive effects

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55
Q

Hydrocortisone

MC:GC Activity
Route of administration
Clinical Use

A

MC:GC Activity: 1:1

Route of administration: TOPICAL, oral, injectable

Clinical Use:

  • Used in PHYSIOLOGIC replacement regimens
  • Must be given several times daily
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56
Q

Prednisone

MC:GC Activity
Route of administration
Clinical Use

A

MC:GC Activity: 1:5

Route of administration: oral (NOT TOPICAL)

Clinical Use: most commonly used oral agent for steroid burst therapy

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57
Q

Dosing considerations with prednisone?

A

MUST be activated to prednisolone in liver**

Cannot be given topically

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58
Q

Dexamethasone

MC:GC Activity
Route of administration
Clinical Use
Adverse effects

A

MC:GC Activity: 0:30 → all GCC activity

Route of administration: oral, injectable, TOPICAL

Clinical Use: used for anti-inflammatory/immunosuppressive actions

  • Most potent anti-inflammatory agent
  • Used in cerebral edema, chemo-induced vomiting
  • Big suppression of ACTH secretion from pituitary

Adverse effects: Significant metabolic side effects

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59
Q

Triamcinolone

A

potent systemic agent with excellent topical activity

NO MC action

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60
Q

Fludrocortisone

A

MC:GC Activity: 125-200:10 → Primarily MC activity without GC / anti-inflammatory activity

High doses can cause hypokalemia

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61
Q

Treatment of Addison’s Disease

A

reat with physiologic replacement therapy (MC and GC replacement required)

Cortisol (GC replacement) + Fludrocortisone (MC replacement) + DHEA (sex steroid replacement for women)

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62
Q

3 main categories of drugs that can be used to treat Cushing’s Syndrome

A

1) ACTH secretion inhibitors
2) Cortisol synthesis inhibitors
3) Cortisol Receptor Antagonist

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63
Q

ACTH secretion inhibitors (2)

A

Cabergoline (D2 agonist)

Pasireotide (SST analog)

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64
Q

Ketoconazole

A

Cortisol synthesis inhibitor

inhibits CYP450 androgen synthesis in testes and inhibits cholesterol → pregnenolone, reduces cortisol synthesis

Adverse effects: headache, N/V, gynecomastia, impotence, reversible hepatotoxicity

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65
Q

Mifepristone

A

Cortisol Receptor Antagonist

-anti-progestational drug that blocks GC receptors at higher doses

Not first line

Used to control hyperglycemia secondary to hypercortisolism

Contraindicated in pregnancy

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66
Q

Treatment of Primary aldosteronism

A

goal is to normalized hypokalemia and BP before surgical removal of tumor

Aldo antagonists: Spironolactone, eplerenone

BP meds: Ca2+ channel blockers, ACEI, ARB

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67
Q

Metyrosine

A

competitive inhibitor of catecholamine synthesis

used to treat pheochromocytoma that is non-surgical

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68
Q

Thyronine

A

backbone of THs with 3, 5, 3’, and 5’ positions that can be iodinated

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69
Q

Thyroxine (T4) vs. T3

A

Thyroxine (T4) = 3, 5, 3’, 5’ tetraiodothyronine

T3 = 3, 5, 3’ triiodothyronine

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70
Q

Iodide trap

A

Membrane pump on basal side of follicular cell promotes accumulation of iodide in thyroid 30-40x concentration in serum

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71
Q

4 steps of iodine uptake by thyroid gland

A

1) Na+/I- symporter + Na/K ATPase on basal side brings I- into cell
2) Iodide diffuses from basal (blood) → apical (lumen) side of follicular cell
3) Iodide oxidized (I- → I2) by thyroid peroxidase
4) Organification of I2 (incorporation of iodide into tyrosyl residues on thyroglobulin) occurs at follicular cell-colloid interface

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72
Q

Thyroperoxidase

A

membrane bound glycoprotein/enzyme in thyroid that catalyzed iodination of thyroglobulin, organification of I2, and coupling of DITs/MITs

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73
Q

Synthesis and Release of Thyroglobulin

A

Thyroglobulin synthesized in RER of follicular cell and transported to Golgi apparatus to be glycosylated and packaged into secretory vesicles

Secretory vesicles released from apical follicular cell into lumen (colloid)

Undergoes iodination and coupling reactions to synthesize TH at tyrosyl residues

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74
Q

Steps of Thyroid Hormone Synthesis

A

thyroperoxidase catalyzes iodination of tyrosyl moieties on TG → mono/di- iodotyrosine (MIT/DIT) formed on TG

Thyroperoxidase also catalyzes coupling of 2 DITs or 1 DIT and 1 MIT to form iodothyronines

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75
Q

Steps of thyroid hormone release

A

Drops of colloid endocytosed into follicular cells → coalesce with lysosomes → lysosomal enzymes act on TG to cleave T4 and T3 from TG

10-20x more T4 removed than T3

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76
Q

Thyroid Hormone Transport

A

Most thyroid hormone in a protein bound form

Some exist in free form (0.03% of T4, and 0.4% of T3)

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77
Q

thyroid hormone in a protein bound form

binds with what 3 proteins?
what is the effect of protein binding?

A

Thyroid binding proteins:

1) Thyroid binding globulin (TBG)
2) Thyroid binding pre-albumin (TBPA)
3) Albumin

Delay, buffer and prolong effects of TH action

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78
Q

half life of T4 vs. T3

A

T ½ for T4 is 7 days, and T3 is 1 day because TBG has a higher affinity for T4

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79
Q

Free thyroid hormone

A

Free form is active form

Must measure plasma TH values for bound or free form in addition to total TH in blood

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80
Q

How is T4 converted to T3?

A

T4 → T3 by 5’-deiodinase in the target cell

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81
Q

Cellular actions of thyroid hormone

A
  • T3 has a higher affinity for TH receptor, so is more active than T4
  • T3/T4 enter cell by ACTIVE TRANSPORT

T4 → T3 by 5’-deiodinase

T3 enters nucleus → interacts with nuclear receptors → T3-receptor complex acts on DNA to direct transcription of specific mRNAs

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82
Q

5 main actions of thyroid hormone

A

1) Metabolic rate
2) Fetal and neonatal brain development
3) TH and GH necessary for normal growth
4) Enhance response to catecholamines
5) Metabolic effects

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83
Q

How does thyroid hormone effect metabolic rate?

A

THs increase basal metabolic rate and increase oxygen consumption = Calorigenic effect

Mostly due to Na/K pump upregulation

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84
Q

Thyroid hormone and catecholamines

A

TH enhances response to catecholamines: TH mimics effects of SNS by increasing number of B-adrenergic receptors = permissive effect

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85
Q

Thyroid hormone and metabolic effects

low/moderate dose of TH vs. high dose of TH

A

Low/Moderate doses of TH → anabolic
-Promote conversion of glucose → glycogen

High doses of TH → catabolic
-Increased fuel consumption, protein breakdown, muscle wasting, glycogenolysis, and lipolysis

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86
Q

TSH and its actions on the thyroid gland

A

TSH → thyroid gland where it interacts with membrane receptor, stimulating thyroid hormone synthesis via increases in cAMP

TSH stimulates:

1) Iodide pump
2) Thyroperoxidase
3) Endocytosis of colloid
4) Iodide organification
5) Coupling of iodotyrosines
6) TG synthesis and its proteolysis following endocytosis
7) Follicular cell proliferation, elongation, and enlargement

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87
Q

3 drugs that block thyroperoxidase and conversion of T4 to T3 in target cells

A

Thioureas, propylthiouracil, methimazole

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88
Q

Signs/Symptoms of Hyperthyroidism (10)

A 
BMR
Nervousness
Pretibial myxedema (Graves)
Heat intolerance
Muscle weakness
Goiter
Palpitations
Exophthalmos (Graves)
Lid retraction (Graves)
Tachycardia
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89
Q

In what cases would you have an elevated total T4/T3, but a normal free T4/T3?

A

Total T4/T3 can be elevated with increases in thyroid binding proteins (e.g. high estrogen states), but free T4/T3 will not be affected

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90
Q

4 causes of high uptake aka “TRUE” Hyperthyroidism

A

Graves Disease (autoimmune thyrotropin receptor antibody)
Toxic adenoma
Toxic multinodular goiter
Tumors of pituitary or thyroid

91
Q

What is low uptake “hyperthyroidism”?

A

release of preformed T3/T4 into blood (NOT TRUE HYPERTHYROIDISM) → thyroid scan will be dark, no need for scan

92
Q

Causes of low uptake “hyperthyroidism” (7)

A

1) Granulomatous thyroiditis (viral) = de Quervain’s → tender thyroid
2) Chronic lymphocytic thyroiditis (Hashimoto’s)
3) Postpartum thyroiditis
4) Radiation, infectious thyroiditis → tender thyroid
5) Drug-induced thyroiditis
6) Excess TH administration (Factitious)
7) Struma ovarii (ovarian tumor that produces thyroid hormones)

93
Q

Grave’s Disease

symptoms?

A

antibodies against TSH receptor → stimulate excess T4/T3 production

Symptoms:
-Ophthalmopathy (thyroid eye disease) and pretibial Myxedema

94
Q

Why does pretibial myxedema and ophthalmopathy occur in Grave’s disease?

A

Occurs due to TSH receptor on fibroblasts → fibroblast overproduction of glycosaminoglycans (GAGs)

95
Q

Tests that indicate Grave’s disease

A

Homogenous uptake, “hot scan” on radioactive iodine scan

Low TSH, high free T4 and T3

96
Q

4 treatment options for Grave’s Disease

A

1) Antithyroid drugs (methimazole, propylthiouracil) → inhibit TH synthesis
2) Beta blockers → reduce systemic hyperadrenergic symptoms
3) Radioactive Iodine
4) Surgery

97
Q

Thyroiditis

A

Types: subacute/granulomatous thyroiditis, postpartum thyroiditis

High release of preformed/stored T3/T4 as thyroid cells are damaged → high free T3, T4 and suppress TSH

Once destruction as resolved, there is no ability to secrete thyroid hormone → high TSH, low thyroid hormone = hypothyroid

NOT true hyperthyroidism (no overproduction of TH)

98
Q

Signs/Symptoms of Hypothyroidism (10)

A 
BMR
Lethargy, weakness
Myxedema
Cold intolerance
Slow speech
Goiter
Hoarseness
Mental slowness
Psychosis
Bradycardia
99
Q

Causes of Hypothyroidism (10)

A

1) Hashimoto’s Thyroiditis (chronic autoimmune)
2) Transient hypothyroidism
3) Iatrogenic: Thyroid surgery/thyroidectomy, Radioactive iodine, External neck irradiation
4) Iodine deficient diet or excess
5) Starvation, severe illness, severe stress, neonatal period (Euthyroid sick syndrome (nonthyroidal illness)
6) Liver or kidney disease (decreased serum protein binding)
7) Drugs (glucocorticoids, propranolol, amiodarone, radiocontrast dyes)
8) Infiltrative disease (TB, hemochromatosis, sarcoidosis, amyloidosis)
9) Cretinism
10) Pituitary tumor (central hypothyroidism)

100
Q

why does Starvation, severe illness, severe stress, neonatal period cause hypothyroidism?

A

→ Inhibit conversion of T4 → T3 (active form) by blocking type 1 or type 2 deiodinase and activating type 3 deiodinase (converts T4 → rT3, inactive form)

101
Q

Hashimoto’s Thyroiditis

A

Autoimmune destruction of thyroid gland

  • most common cause of hypothyroidism in regions where iodine levels are adequate
  • associated with HLA-DR5

Autoimmune destruction of follicular cells → initial dumping of thyroid hormone out of cells (hyperthyroidism) and progress to hypothyroidism

102
Q

Cretinism

A

deficiency in neonates and infants

severe mental and growth retardation

short stature, skeletal abnormalities, coarse facial features, enlarged tongue, umbilical hernia

-can be caused by maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter, and iodine deficiency

103
Q

__________ and __________ antibodies are often present in Hashimoto Thyroditis as a sign of thyroid damage

A

Antithyroglobulin

Antithyroid peroxidase antibodies

104
Q

Histological presentation of Hashimoto’s thyroditis (2 main features

A

chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles)

105
Q

Increased risk for _________ with Hashimotos thyroditis

A

B-cell (marginal zone) lymphoma

presents as an enlarging thyroid glans late in disease course

106
Q

Subacute granulomatous (De Quervain) Thyroditis

A

Granulomatous thyroiditis that follows a viral infection

Presents as a tender thyroid** with transiet hyperthyroidism

Self-limited
*rare progression to hypothyroidism

107
Q

Riedel fibrosing thyroiditis

A

chronic inflammation with extensive fibrosis of thyroid gland

  • presents as hypothyroidism + “hard as wood”, non-tender thyroid gland
  • fibrosis may extend to involve local structures
  • mimics anaplastic carcinoma
  • classicaly seen in young female patient
108
Q

Myxedema Coma

A

Complication of chronic, severe hypothyroidism (typically Hashimoto)

true endocrine emergency - decrease CO, bradycardia, respiratory depression, edema, AMS, hypothermia, metabolic derangements

High mortality rate

109
Q

3 main tests used to evaluate thyroid dysfunction

A

1) Thyroid Stimulating Hormone
2) Free T4 (not free T3)
3) Radioactive iodine uptake and scan

110
Q

TSH testing:

Primary hypothyroidism vs. primary hyperthyroidism

when is TSH level unreliable?

A

best test to screen for thyroid dysfunction

Primary hypothyroidism → elevated TSH, low thyroid hormone
–> Lack of negative feedback by thyroid hormone

Primary hyperthyroidism → low TSH
–> Excessive negative feedback by thyroid hormone

CANNOT rely on TSH when pituitary gland is abnormal

111
Q

When should you check a T4?

A

Check T4 if TSH is low

112
Q

Radioactive iodine uptake and scan

Normal/elevated iodine uptake in setting of low TSH → ?

Low iodine uptake in setting of low TSH → ?

A

Normal/elevated iodine uptake in setting of low TSH → autonomous production of thyroid hormone = true hyperthyroid state

Low iodine uptake in setting of low TSH → thyroid hormone excess due to high release of preformed thyroid hormone → destructive / inflammatory etiology (e.g. early Hashimoto’s, thyroditis)

113
Q

thyroid adenoma

A

Benign thyroid nodule

Typically solitary nodule

Must carefully evaluate capsule (with biopsy) - cannot be differentiated follicular adenoma from follicular carcinoma with FNA

114
Q

Papillary Thyroid Carcinoma

A
  • Most common type of thyroid carcinoma (80%)
  • Associated with ionizing radiation in childhood
  • Well-differentiated
  • Lymphatic spread
  • Excellent prognosis
115
Q

Follicular Thyroid Carcinoma

A
  • Malignant proliferation of follicles surrounded by fibrous capsule WITH INVASION THROUGH CAPSULE = hallmark
  • -> can distinguish from follicular adenoma (via biopsy, NOT FNA)

-metastasizes HEMATOGENOUSLY

116
Q

Anaplastic Thyroid Carcinoma

A
  • Highly invasive undifferentiated malignant tumor of thyroid
  • seen in elderly
  • very aggressive, poor survival
  • rapidly growing mass with necrosis and hemorrhage
117
Q

Medullary Thyroid Carcinoma is a malignant proliferation of what cell type?

what will it stain with immunostain?

what can deposit in the tumor?

A

Malignant proliferation of parafollicular C cells (neuroendocrine cells that secrete calcitonin)

  • can get amyloid deposition of calcitonin in tumor
  • Immunostains: thyroglobulin -, calcitonin +, chromogranin +

Associated with MEN2

118
Q

Papillary Thyroid Carcinoma

Histology - 3 main features

A

1) papillae lined by cells with clear “ORPHAN ANNIE EYE” nuclei
2) Nuclear grooves
3) Papillae often associated with psammoma bodies

119
Q

Anatomic imaging modalities (3)

A

Detect or characterize palpable or incidentally found thyroid nodule on other modalities

1) Ultrasound
2) CT Neck
3) MRI

120
Q

Ultrasound used for work up of thyroid disease how?

A

no radiation, real time, doppler capability

  • Best modality to detect/characterize thyroid nodule
  • Best modality to detect lymph node metastasis in post-op patient of thyroid cancer

Used for real time guidance for FNA

121
Q

CT Neck used for work up of thyroid disease how?

A

Useful to define local extension of cancer in adjacent structures

Detect abnormal lymph nodes in areas not visualized by US

Distant metastasis

122
Q

MRI used for work up of thyroid disease how?

A

Useful in identifying infiltrative disease particularly in post-therapy neck where anatomy is distorted

Detection of invasion of adjacent structures and deep nodal disease

NOT used to detect or characterize thyroid nodule

123
Q

Iodine scanning can be used for what in working up thyroid dysfunction?

A

Functional imaging

Evaluate for function of thyroid gland or nodule in patient with abnormal thyroid function

Evaluate for distant metastatic disease

124
Q

I-123 vs. I-131 iodine scans

A

I-123 scan: evaluate function of thyroid gland and thyroid nodule in patient with abnormal thyroid function (diagnostic only)

I-131 scan: diagnostic and therapeutic role

  • Detect local/distant thyroid cancer metastasis
  • Treatment of hyperthyroidism and well differentiated thyroid cancer
125
Q

On a CT neck, the normal thyroid is _________ on noncontrast and _________ with IV contrast

A

Hyperdens on noncontrast

Hypervascular with IV contrast

126
Q

Fetal thyroid gland arises from 2 distinct embryonic lineages

A

1) Follicular cells (endodermal pharynx) → produce thyroxine (thyroid hormone)
2) Parafollicular cells (neural crest) → produce calcitonin

127
Q

After descent, thyroid follicular cells differentiate to express genes essential for ________________

A

thyroid hormone synthesis

128
Q

Thyroid follicular cells trap iodide and secrete thyroid hormone by ________ wks.

Maternal ______ crosses the placenta for hormone synthesis

______ and ______ levels gradually increase to term

A

Trap iodide, secrete thyroid hormone, and TSH by 10-12 wks

Maternal iodine crosses placenta for hormone synthesis

TSH and T4 levels gradually increase to term

129
Q

Hypothalamus-Pituitary-Thyroid axis is functional with feedback control by __________ wks

A

25 weeks

130
Q

Thyroid gland originates as proliferation of _________ cells on median surface of __________ between ____ and ____ arches

Initially hollow → becomes solid and bilobed

A

Thyroid gland originates as proliferation of endodermal epithelial cells on median surface of pharyngeal floor between 1st and 2nd arches

Initially hollow → becomes solid and bilobed

131
Q

Thyroid gland is connected to the ______ via the ________ as it descends. It completes this descent by the ______ week.

two problems that can arise due to thyroglossal duct problems?

A

Thyroid connected to TONGUE via THYROGLOSSAL DUCT as it descends

Completes descent in 7th gestational week

Can have arrested descent of thyroid or thyroid duct cyst

132
Q

What if fetus doesn’t make thyroid hormone? How can fetus still get some thyroid hormone?

A

Placenta allows small amount of maternal T4 and iodine across → maternal T4 converted to T3 by type II deiodinase in fetal brain
→ minimizes adverse effects of fetal hypothyroidism

133
Q

Transcription Factors Important for Thyroid Development (3)

A

1) PAX8
2) TITF1
3) TITF2

134
Q

PAX8

A

paired box gene 8 transcription factor

Mutation causes thyroid dysgenesis

AD pattern of inheritance

Phenotypes vary from mild to severe hypoplasia (compensated or overt hypothyroidism)

Can be associated with renal agenesis

135
Q

TITF1

A

Mutation can cause thyroid dysgenesis

Also expressed in lung, forebrain, and pituitary gland

Heterozygous mutation → CH, respiratory distress, neuro disorders

136
Q

TITF2

A

thyroid transcription factor 2

Mutation can cause thyroid dysgenesis

Homozygous mutation → Bamforth Lazarus Syndrome

137
Q

Bamforth Lazarus Syndrome

A

Congenital Hyothyroidism, cleft palate, spiky hair, bifid epiglottis, choanal atresia

138
Q

Congenital hypothyroidism

A

lack of thyroid hormones present from birth

If not detected/treated early, can cause irreversible neurological problems and poor growth

Associated with other congenital abnormalities

139
Q

4 causes of Congenital hypothyroidism

A

1) Thyroid Dysgenesis
2) Thyroid dyshormonogenesis
3) TSH resistance
4) Transient forms
5) Central Hypothyroidism

140
Q

Thyroid Dysgenesis

  • defect in what?
  • causes ____% of congenital hypothyroidism
  • due to _____, ______ or ______ (most common)
  • female:male ratio?

-caused by defects in what transcription factors?

A

defect in thyroid gland development

85% of congenital hypothyroidism

Aplasia, hypoplasia, or **ectopy (most common - thyroid gland arrests in descent)

Female:Male 2:1

Caused by transcription factor defects (PAX8, TITF1, TITF2)

141
Q

Thyroid dyshormonogenesis

  • defect in what?
  • causes ____% of congenital hypothyroidism
  • can be caused by a mutation in what genes?
A

defect in thyroid hormone synthesis

10-15% of congenital hypothyroidism

Can be caused by mutations in genes coding for proteins involved in thyroid hormone synthesis

Most common is thyroid peroxidase gene mutation

AR inheritance

Goiter may be present

142
Q

Pendred Syndrome

A

Type of thyroid dyshormonogenesis

AR mutation in SLC26A4 encoding pendrin protein that mediates iodide efflux from follicular cell to colloid

Goiter

Sensorineural congenital deafness (dilated semicircular canals on CT)

Thyroid phenotype mild and depends on nutritional iodine intake

Does not present in newborn period

143
Q

TSH resistance

A

mutation in TSH-R transmembrane receptor on surface of follicular cells

Mediated effects of TSH

Critical for development and function of thyroid gland

144
Q

TSH resistance:

  • heterozygous loss of function mutation –> ?
  • Homozygous TSH-R mutations →
A

Heterozygous loss of function mutations → partial resistance with normal size gland and TSH elevation

Homozygous TSH-R mutations → congenital hypothyroidism with hypoplastic gland and decreased T4 synthesis

145
Q

Transient forms of congenital hypothyroidism (4)

A

1) Maternal TSH-R blocking abs
2) Maternal iodine deficiency or excess
3) Maternal radioiodine administration
4) Maternal medications (amiodarone, propylthiouracil, methimazole)

146
Q

Central Hypothyroidism

A

(Hypothalamic/Pituitary Deficiencies)

Usually in setting of multiple pituitary hormone deficiency especially growth hormone deficiency

Must evaluate other pit. hormones and obtain cranial MRI

147
Q

Treatment of congenital hypothyroidism

A

start treatment with levothyroxine AS EARLY AS POSSIBLE

148
Q

Newborn screening for congenital hypothyroidism

A

Best to do after 2-3 days of age due to initial TSH surge after birth

1) Primary T4 screening (most common)
or
2) Primary TSH screening

Follow screening with confirmatory labs

149
Q

Primary T4 screening in newborn screen

A

If T4 in lowest 10% of results on a given day → measure TSH

  • If TSH > 20 = abnormal → call PCP
  • If TSH < 20 could still be abnormal, but will not call PCP

Total T4 = bound + free

Can get inaccurate results in presence of extreme variations in concentrations of thyroid-binding proteins

150
Q

Normal TSH secretion in first week of life:

A

Within 30 minutes of birth, TSH rapidly peaks to 60-80 uU/ml, then decreases → peak in T4 and T3 levels by 24 hours

151
Q

T3-Uptake screening:

T3 uptake and T4 in SAME direction → ?

T3 uptake and T4 in OPPOSITE direction →?

A

used to differentiate central hypothyroidism and thyroid binding globulin deficiency

T3 uptake and T4 in SAME direction → thyroid disease
-Low uptake and low T4 = hypothyroid

T3 uptake and T4 in OPPOSITE direction → TBG abnormality
-High uptake and lw T4 → TBG deficient

152
Q

Signs/Symptoms of Congenital Hypothyroidism (8)

A

**Baby appears normal at first - sx may not develop for weeks

Large posterior fontanel

Prolonged jaundice

Macroglossia

Umbilical hernia

Hypotonia

Feeding difficulties

Hoarse cry

153
Q

Thyroid hormone reversibly bound in plasma to thyroid-binding-globulin (TBG), and only unbound hormone has metabolic activity

what drugs can increase TBG binding? (3)
what drugs can decrease TBG binding? (5)

A
  • Increase binding with: estrogens, SERMs, Tamoxifen
  • Decreased binding with: salicylates, anti seizure meds (phenytoin, carbamazepine), androgens, glucocorticoids, furosemide
154
Q

T4 must be activated to T3, biologically active thyroid hormone, done by _________ in _______

A

T4 must be activated to T3, biologically active thyroid hormone, done by 5’-deiodinase in liver

155
Q

drugs that can decrease activity of 5-deiodinase (4)

A

glucocorticoids, B-blockers, propylthiouracil, amiodarone

156
Q

Levothyroxine (T4)

A

drug of choice for thyroid hormone replacement therapy

Use: hypothyroidism, myxedema coma (end state of untreated hypothyroidism)

Narrow therapeutic index
Takes 6-8 weeks of maintenance dose to reach steady-state plasma levels

Oral or IV, generic and cheap

Use same levothyroxine product throughout treatment for any individual patient

157
Q

Levothyroxine (T4)

Adverse reactions (1) + caution starting this med in what patients?

A

symptoms of hyperthyroidism

Use caution initiating therapy if underlying cardiac disease

158
Q

Bioavailability of Levothyroxine can be modified by impaired absorption caused by what drugs? (3)

A

Metal ions (antacids, calcium and iron supplements)

Ciprofloxacin

bile acid sequestrants

159
Q

Liothyronine

A

(T3):
Well absorbed, rapid action, shorter duration
Allows for quicker dosage adjustments
NOT recommended for routine replacement (plasma level fluctuates)
Higher potential for cardiovascular side effects during initiation of therapy
More expensive

160
Q

Liotrix

A

(T3, T4 mixture):

More expensive, no real advantage, not really used

161
Q

Thyroid USP

A

porcine thyroid extract

Disadvantages: protein antigenicity, product instability, variable T4/T3 ratio may produce unexpected toxicity

Use in hypothyroidism NOT recommended

162
Q

Thionamides

drug names?
Mechanism?
combine with what other med?

A

Methimazole, Propylthiouracil (PTU)

Mechanism: block iodine organification AND coupling of iodotyrosines → prevent T4/T3 synthesis

Pros: leaves gland intact

Combine with B-blocker (Propranolol blocks T4 → T3 conversion)

163
Q

Methimazole

A

generally preferred over PTU
Efficacy at lower doses
Once-daily dosing
Fewer side effects

164
Q

PTU preferred in __________

A

pregnancy

165
Q

PTU and Methimazole

Side effects

A

Caution in pregnancy (can cross placenta) - PTU more protein bound so crosses less freely

Pruritic rash, GI intolerance, arthralgias

Agranulocytosis

Rare hepatotoxicity

166
Q

Iodides (I-)

mechanism?
use?
disadvantages?

A

Mechanism: inhibit hormone synthesis and hormone release through inhibition of thyroglobulin proteolysis

Use: Rapid effects, used in thyrotoxicosis and thyroid storm

Disadvantages: variable effects, can worsen hyperthyroidism

167
Q

Radioactive iodine (131I)

Mechanism?
Advantages?
Disadvantages?

A

Concentrated in thyroid → slow inflammatory process that destroys parenchyma of gland over weeks to months

Advantages: easy administration (oral), effective, inexpensive, no pain
Permanent resolution of hyperthyroidism

Disadvantages: slow onset of effects, radiation thyroiditis, may worsen ophthalmopathy, can cause hypothyroidism (80% require replacement therapy)

168
Q

Treatment of Graves’ Disease:

1) ________ and _________ → modify tissue response, symptomatic improvement
2) ________ and _________ → interfere with hormone production
3) ________ and _________ → glandular destruction

A

1) B-blockers, corticosteroids → modify tissue response, symptomatic improvement
2) Thioamides, iodides → interfere with hormone production
3) Surgery, radioactive iodine → glandular destruction

169
Q

Treatment of Myxedema Coma (end state of untreated hypothyroidism)

A

1) Large IV loading dose T4 + daily IV dosing

2) Hydrocortisone to prevent adrenal crisis as T4 increase may increase endogenous hydrocortisone metabolism

170
Q

Treatment of thyroid storm:

4 meds and why?

A

Beta-Blockers: Propranolol → control CV symptoms

Sodium iodide IV + Potassium iodide → slow RELEASE of hormones

PTU → block hormone synthesis and T4 → T3 conversion

Hydrocortisone → block T4 to T3 conversion

171
Q

Thyroidectomy

A

rarely used due to effective radioactive treatment

Advantage: rapid, permanent cure of hyperthyroidism

172
Q

Diabetes and mood:

depression
bipolar disorders

A

Depression: 2-3x general population, worsens control of blood sugar

Bipolar Disorders: increased risk of also having DM2

  • Higher rate of obesity for pts with bipolar
  • Treatments for bipolar disorder → metabolic effects, weight gain
  • Sleep apnea worsens insulin resistance
173
Q

Hypercortisolemia and psych symptoms (6)

A

Psych symptoms may predate physical:

Depressive symptoms
Anxiety
Hypomanic/manic symptoms
Psychosis
Memory problems and other cognitive symptoms
174
Q

what can occur in both hypo and hypercalcemia?

A

PSYCHOSIS**

175
Q

Hyperparathyroidism with hypercalcemia:

pscyh symptoms?

A

Common: irritability, low mood, apathy, lethargy
Severe: delirium, psychosis, catatonia, coma

176
Q

Hypocalcemia

psych symptoms

A

Common: anxiety, paresthesias, irritability
Severe: psychosis, manic symptoms, tetany, seizures

177
Q

Addison’s disease

and psych symptoms

A

primary adrenal insufficiency

Psych symptoms: apathy, anhedonia, fatigue, depression

178
Q

Acromegaly and psych symptoms

A

increased growth hormone

Psychiatric symptoms: irritability, mood lability, depressive symptoms, personality changes

179
Q

Thyroid problems and psych symptoms interact how?

A

Thyroid hormone interacts with NE, serotonin, dopamine

Thyroid hormones appear to be capable of modulating phenotypic expression of illness

180
Q

Hypothyroidism and psych symptoms

A

depression*, lethargy, forgetfulness (can be confused with dementia especially in older women), psychosis (later stages)

**Can have subclinical hypothyroidism unresponsive to antidepressants, and thyroid replacement may improve outcomes

181
Q

Hyperthyroidism and psych symptoms

A

anxiety disorder, depressive disorder, mania when thyrotoxic

182
Q

In Worrisome Growth you are worried about children having abnormal __________ or __________

A

height or growth velocity

183
Q

What is considered worrisome growth for height?

A

short stature, height below 2 SD (3%) for age and gender OR height more than 3.5 inches below the midparental target height

184
Q

What is considered worrisome growth for growth velocity

A

abnormally slow linear growth velocity or dropping across two major centile lines on the growth chart

185
Q

Midparental target

A

97% of children fall within 3.5 inches of target

Boys → (Mom height + 5 inches + Dad height) / 2
Girls → (Dad height - 5 inches + Mom height) / 2

186
Q

Skeletal maturation

A

direct correlation between degree of skeletal maturation and time of epiphyseal closure

Greater bone age delay = longer time before epiphyseal fusion ceases growth

Can be used to predict height by using child’s height and bone age BUT predictions NOT accurate in children with growth disorders

187
Q

Normal variant of short stature (2)

A

1) Familial short stature

2) Constitutional growth delay

188
Q

Familial short stature

A

children who have normal growth velocity and height that are within normal limits for parents’ heights

Initially will have decrease in growth rate between 6 and 18 months of age –> then track growth chart, but just lower than other people because their parents are short

189
Q

Constitutional growth delay

A

aka “late bloomers”

born at normal weight/length with growth deceleration during first 2 years of life –> followed by normal growth paralleling lower percentile curve throughout prepubertal years

Should NOT be falling off after age 2-3 yrs

Skeletal maturation delayed**

Catch-up growth achieved by late puberty and delayed fusion of growth plates

Usually end up at lower end of normal height range for families

190
Q

Treatment of Constitutional growth delay

A

Boys: testosterone if bone age > 11.5 yrs
Girls: estrogen

191
Q

Failure to thrive

A

infants and toddlers < 2 years of age with:

Deceleration of weight gain < 3% or fall in weight across 2 or more major percentiles

-Typically primary weight issue with later height drop off

Non-organic causes most common (poor nutrition, psychosocial factors)

May look like constitutional growth delay

192
Q

Nutritional growth retardation

A

linear growth stunting from poor weight gain in children > 2 yrs of age

May be secondary to systemic illnesses (celiac, IBD, CF), or stimulant medications

Hard to distinguish from constitutional growth delay/thinness

Weight typically falls off before height

193
Q

Hypothyroidism and worrisome growth

A

profound growth failure, lacks common sx of hypothyroid seen in adults

Growth chart patterns: can have profound drop off on height + weight drop off

194
Q

Cushing’s and worrisome growth

A

excessive weight gain, with falling off on height

195
Q

small for gestational age

A

< 2SD for birth weight or length

Most healthy infants with SGH achieve catch-up in height by 2yr

Typically grow along a stable trajectory, but have height projection less than their genetic target

May have early or rapid puberty (compromises height)

**No delayed bone age - INTRINSIC short stature

196
Q

Treatment for small for gestational age (SGA)

A

growth hormone treatment for kids who fail to have catch-up growth by age 2 years

197
Q

Pathological causes of short stature

A

Nutritional (zinc, iron, anorexia, IBD, celiac disease, CF)

Endocrine:

1) Hypothyroid
2) Growth hormone deficiency
3) Cushing
4) Rickets
* *Two or more endocrine deficiency = BRAIN TUMOR until proven otherwise

Chromosomal:

1) Turner syndrome
2) Down syndrome
3) Prader-Willi Syndrome: GH deficient
4) Noonan syndrome

Others: skeletal dysplasias, metabolic, chronic diseases, psychosocial deprivation, drugs (stimulants, glucocorticoids)

198
Q

Growth hormone deficiency

congenital and acquired causes

A

Congenital causes: Hypothalamic-pituitary malformations

1) Holoprosencephaly/Schizencephaly
2) Isolated cleft lip or palate
3) Septo-optic-dysplasia
4) Optic nerve hypoplasia
5) Empty sella syndrome

Acquired: trauma, CNS infection, hypophysitis, CNS tumors (craniopharyngioma, germinoma), cranial irradiation

199
Q

Growth hormone deficiency

presentation

A

1) abnormal growth velocity with exclusion of other causes
2) Decreased muscle build
3) Increased subcutaneous fat (truncal)
4) Face immature for age
5) Prominent forehead, depressed midface
6) Small phallus (males)
7) Other midline facial defects
8) Prolonged jaundice +/- hypoglycemia in newborn period

200
Q

Evaluation of growth hormone deficiency for worrisome growth (4)

A

1) Bone age

2) IGF-1
May be reduced due to malnutrition regardless of GH status
Can test IGFBP-3 instead - less affected by nutrition

3) Stimulation testing - clonidine, arginine, glucagon, L-dopa
4) MRI to evaluate for brain tumor, empty sella, etc. - high suspicion with other hormone deficiencies for tumor

201
Q

Turner Syndrome (45X)

A

Haploinsufficiency of SHOX genes → Skeletal and growth abnormalities

Most common sex chromosome abnormality of females (1/2000)

No bone age delay (intrinsic short stature)

Will end up short, even with treatment with GH - no potential to reach height normal for their family

Not due to GH deficiency, due to SHOX gene deficiency

202
Q

Presentation of turner syndrome

A

1) Short stature
2) Increased carrying angle
3) Short neck
4) Micro or retrognathia
5) Lymphatic obstruction (lymphedema)
6) Low hairline
7) Webbed neck
8) Cardiac abnormalities (bicuspid aortic valve, coarctation or aorta)
9) Renal - horseshoe kidney
10) Ovarian insufficiency
11) Hypothyroidism / celiac disease
Otitis media, hearing loss
12) Nonverbal learning disability

203
Q

Short stature in Turner Syndrome

A

(final height 20 cm < target height if untreated)

Significant initial drop off on turner syndrome initially, and then have a secondary fall off around 5-6yrs, but if they have tall parents can be around 10-12yrs (can go unnoticed)

204
Q

Treatment of growth in Turner Syndrome

A

growth hormone therapy (significantly improves growth and final adult height)
Start treatment as early as possible

205
Q

8 tests you can do when evaluating worrisome growth

A

1) Bone age (left hand and wrist) → determine growth potential
2) Metabolic panel → rule out RTA, rickets
3) CBC → rule out anemia, chronic disease, skeletal dysplasia
4) TSH and T4
5) IGF-1 or IGFBP-3
6) Karyotype in girls → rule out Turner
7) TTG and IgA → rule out Celiac
8) ESR → rule out IBD

206
Q

“FDA-approved” uses of growth hormone (9)

A 
1985 - GH deficiency
1993 - chronic renal insufficiency
1996 - Adult growth hormone deficiency
1997 - Turner Syndrome
2000 - Prader-Willi Syndrome
2001 - small for gestational age (< 2 SDs)
2003 - idiopathic short stature
2006 - SHOX deficiency
2007 - Noonan syndrome
207
Q

Side effects of GH treatment

A

slipped capital femoral epiphysis (hip or knee pain), intracranial hypertension (pseudotumor cerebri), insulin resistance

208
Q

Determining a Good Clinical Practice Guideline:

8 steps/points of assessment

A

1) Transparency
2) Management of conflict of interests
3) Guideline group composition
4) Collaboration and coordination between systemic review and guideline development
5) Evidence foundation for recommendation
Judge certainty of net benefit based on evidence
6) Articulation of recommendation
7) External review
8) Update

209
Q

____________ should be the first thing to look for when you are looking for how to treat a patient

A

Evidence based practice guideline

210
Q

What is the best research evidence?

A

systematic reviews of RCTs

211
Q

Systematic reviews

A

summary of best available evidence to address a focused question

212
Q

Standard methods designed to reduce bias in systematic reviews

A

1) Focused question
2) Sources/search explicit, comprehensive
3) Selection is criterion based
4) Appraisal is critical
5) Synthesis is systematic
6) Inferences are evidence based

213
Q

How do you critically appraise something?

3 questions to ask

A

Are results valid

Are valid results meaningful

Are the valid, meaningful results relevant to my patient

214
Q

What kind of error can you have in a systematic review?

A

systematic error (bias) that causes results to be consistently distorted in one direction because of nonrandom factors

215
Q

Two main types of bias in systematic reviews:

A

1) Publication bias

2) Location bias

216
Q

Publication bias

A

tendency for published studies to differ systematically in their results from unpublished studies → significant studies more likely to be published

217
Q

Location bias

A

tendency for high profile, widely disseminated studies to differ systematically in their results from low profile, less widely disseminated studies

Significant studies are easier to find

218
Q

How to reduce publication and location bias? (4)

A

Avoid language restrictions

Search more than one electronic database

Search other types of documents

Check references of other studies

Contact experts or organizations

219
Q

Meta-analysis is a ________ synthesis of data

A

Meta-analysis: QUANTITATIVE synthesis of data

220
Q

Meta-analysis

A

STATISTICAL method for combining effect estimates of multiple studies to produce a single common estimate of effect

Improves precision by combining all available data

May or may NOT be part of a systematic review

Studies must have same outcome and be measured in similar ways

221
Q

Disadvantages of meta-analysis

A

Does not control for bias

May inappropriately combine heterogeneous studies (adding apples to apples)

Problems in interpretation

222
Q

Narrative review articles

A

structured summary and discussion of individual study characteristics and effect estimates

ALL relevant results should be presented

Use structured approach to presentation

223
Q

How to deal with statistical heterogeneity: (4 strategies)

A

1) Do not pool at all
2) Ignore heterogeneity (use fixed effect model)
3) Allow for heterogeneity (use random effects model)
4) Explore heterogeneity through special statistical methods

DEMS (10 decks)

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